. The long-term objectives of these studies are to define whether in vitro isolation of nucleoside resistant human immunodeficiency virus type 1 (HIV-1) from patients treated with zidovudine (AZT) or dideoxyinosine (ddI) correlates with disease progression, and to directly detect the mutations in HIV-1 reverse transcriptase (RT) that cause clinically significant AZT resistance. The specific aims are to identify and characterize AZT- and ddI-resistant clinical isolates of HIV-1 and to evaluate the clinical significance of nucleoside resistant HIV isolates and develop an RNA/PCR assay for nucleoside resistant RT genomes in plasma. Finally, it is planned to evaluate the enzymology of AZT resistant RT in order to explain the discrepancy between AZT resistant virion infectivity and the normal RT susceptibility to AZT-TP (triphosphate) in standard assays in vitro.